Home » ANATOMICAL AND PHYSIOLOGICAL FEATURES OF THE DEVELOPMENT AND STRUCTURE OF TISSUES AND ORGANS SCHLD IN CHILDREN

ANATOMICAL AND PHYSIOLOGICAL FEATURES OF THE DEVELOPMENT AND STRUCTURE OF TISSUES AND ORGANS SCHLD IN CHILDREN

June 19, 2024

ANATOMICAL AND PHYSIOLOGICAL FEATURES OF THE DEVELOPMENT AND STRUCTURE OF TISSUES AND ORGANS SCHLD IN CHILDREN.

ANESTHESIA SURGERY IN SCHLD IN CHILDREN IN AMBULATORY AND HOSPITAL

Local anasthetics.

• Role:

–Decrease intraoperative and postoperative pain

–Decrease amount of general anesthetics used in the OR

–Increase patients cooperation

–Diagnostic testing/examination

Anatomical considerations:

• Trigeminal nerve:

– Sensory divisions:

• Ophthalmic division V1

• Maxillary division V2

• Mandibular division V3

– Motor division:

• Masticatory- masseter, temporalis, medial and lateral pterygoids

• Mylohyoid

• Anterior belly of the digastric

• Tensor tympani

• Tensor veli palatini

Maxillary Division (V2):

• Exits the cranium via foramen rotundum of the greater wing of the sphenoid

• Travels at the superior most aspect of the pterygopalatine fossa just posterior to the

maxilla

• Branches divided by location:

– Inter-cranial

– Pterygopalatine

– Infraorbital

– Facial

Maxillary Division (V2):

• Branches:

–Within the cranium- middle meningeal nerve providing sensory innervation to the dura mater

–Within the pterygopalatine fossa-

• Zygomatic nerve

• Pterygopalatine nerves

• Posterior superior alveolar nerve

Maxillary Division (V2):

• Within the pterygopalatine fossa- –

– Zygomatic nerve:

• Zygomaticofacial nerve- skin to cheek prominence

• Zygomaticotemporal nerve- skin to lateral forehead

–Pterygopalatine nerves:

• Serves as communication for the pterygopalatine ganglion and the maxillary nerve • • Carries postganglionic secretomotor fibers through the zygomatic branch to the lacrimal gland

Maxillary Division (V2):

• Within the pterygopalatine fossa-

– Pterygopalatine nerves:

• Orbital branches- – supplies periosteum of the orbits

• Nasal branches- – supplies mucous membranes of superior and middle conchae, lining of posterior ethmoid sinuses, and posterior nasal septum.

–Nasopalatine nerve- travels across the roof of nasal cavity giving branches off to the anterior nasal septum and floor of nose. Enters incisive foramen and provides palatal gingival innervation to the premaxilla

Maxillary Division (V2):

• Within the pterygopalatine fossa-

–Pterygopalatine nerves:

• Palatine branches- – greater (anterior) and lesser (middle or posterior) palatine nerves

–Greater palatine: travels through the pterygopalatine canal and enters the palate via the greater palatine foramen. Innervates palatal tissue from premolars to soft palate. Lies 1cm medial from 2nd molar region

– – Lesser palatine: emerges from lesser palatine foramen and innervates the mucous membranes of the soft palate and parts of the tonsillar region \

Maxillary Division (V2):

• Within the pterygopalatine fossa-

–Pterygopalatine nerves:

• Pharyngeal branch- exits the pterygopalatine ganglion and travels through the pharyngeal canal. Innervates mucosa of the portions of the nasal pharynx

• Posterior superior alveolar nerve (PSA): branches from V2 prior to entrance into infraorbital groove. Innervates posterior maxillary alveolus, periodontal ligament, buccal gingiva, and pulpal tissue (only for 1st, 2nd and 3rd molars)

Maxillary Division (V2):

• Infraorbital canal branches:

–Middle superior alveolar (MSA):

• Provides innervation to the maxillary alveolus, buccal gingiva, periodontal ligament, and pulpal tissue for the premolars only

–Anterior superior alveolar (ASA):

• Provides innervation to the maxillary alveolus, buccal gingiva, periodontal ligament, and pulpal tissue for the canines, lateral and central incisors

• Branches 6- 8mm posterior to the infraorbital nerve exit from infraorbital foramen Maxillary Division (V2):

• Facial branches:

–Emerges from the infraorbital foramen

–Branches consist of:

• Inferior palpebral- lower eyelid

• External nasal- lateral skin of nose

• Superior labial branch- skin and mucosa

Mandibular division (V3):

• Largest branch of the trigeminal nerve

• Composed of sensory and motor roots

• Sensory root:

–Originates at inferior border of trigeminal ganglion

• Motor root:

–Arises in motor cells located in the pons and medulla

–Lies medial to the sensory root

Mandibular division (V3):

• Branches:

–The sensory and motor roots emerge from the foramen ovale of the greater wing of the sphenoid

–Initially merge outside of the skull and divide about 2 -3mm inferiorly

–Branches:

• Branches of the undivided nerve

• Branches of the anterior division

• Branches of the posterior division

Mandibular division (V3):

• Branches of the undivided nerve:

–Nervus spinosus- innervates mastoids and dura

–Medial pterygoid- innervates medial pterygoid muscle

• Branches into

–Tensor veli palatini

–Tensor tympani

Mandibular division (V3):

• Branches of the anterior division:

–Buccal nerve (long buccal and buccinator):

• Travels anteriorly and lateral to the lateral pterygoid muscle

• Gives branches to the deep temporal (temporalis muscle), masseter, and lateral pterygoid muscle

Mandibular division (V3):

• Branches of the anterior division:

–Buccal nerve (long buccal and buccinator):

• Continues to travel in antero- lateral direction

• At level of the mandibular 3rd molar, branches exit through the buccinator and provide innervation to the skin of the cheek

• Branches also stay within the retromandibular triangle providing sensory innervation to the buccal gingiva of the mandibular molars and buccal vestibule

Mandibular division (V3):

• Branches of the posterior division:

–Travels inferior and medial to the lateral pterygoid

• Divisions:

–Auriculotemporal

–Lingual

–Inferior alveolar

Mandibular division (V3):

• Branches of the posterior division:

– Auriculotemporal: all sensory

• Transverses the upper part of the parotid gland and posterior portion of the zygomatic arch

• Branches:

– Communicates with facial nerve to provide sensory innervation to the skin over areas of the zygomatic, buccal, and mandibular

–Communicates with the otic ganglion for sensory, secretory, and vasomotor fibers to the parotid

Mandibular division (V3):

• Branches of the posterior division:

–Auriculotemporal: all sensory

• Branches:

–Anterior auricular- skin over helix and tragus

–External auditory meatus- – skin over meatus and tympanic membrane

–Articular- posterior TMJ

–Superficial temporal- skin over temporal region

Mandibular division (V3):

• Branches of the posterior division:

–Lingual:

• Lies between ramus and medial pterygoid within the pterygomandibular raphe

• Lies inferior and medial to the mandibular 3rd molar alveolus

• Provides sensation to anterior 2/3rds of tongue, lingual gingiva, floor of mouth mucosa, and gustation (chorda tympani)

Mandibular division (V3):

• Branches of the posterior division:

–Inferior alveolar:

• Travels medial to the lateral pterygoid and latero- posterior to the lingual nerve

• Enters mandible at the lingula

• Accompanied by the inferior alveolar artery and vein (artery anterior to nerve)

• Travels within the inferior alveolar canal until the mental foramen

• Mylohyoid nerve- motor branch prior to entry into lingula

Mandibular division (V3):

• Branches of the posterior division:

–Inferior alveolar:

• Provides innervation to the mandibular alveolus, buccal gingiva from premolar teeth anteriorly, and the pulpal tissue of all mandibular teeth on side blocked

• Terminal branches

–Incisive nerve- – remains within inferior alveolar canal from mental foramen to midline

–Mental nerve- exits mental foramen and divides into 3 branches to innervate the skin of the chin, lower lip and labial mucosa

Local anesthetic instruments:

• Anesthetic carpules

• Syringe

• Needle

• Mouth props

• Retractors

Maxillary anesthesia:

• 3 major types of injections can be performed in the maxilla for pain control

–Local infiltration

–Field block

–Nerve block

Maxillary anesthesia:

• Infiltration:

–Able to be performed in the maxilla due to the thin cortical nature of the bone

–Involves injecting to tissue immediately around surgical site

• Supraperiosteal injections

• Intraseptal injections

• Periodontal ligament injections

Maxillary anesthesia:

• Field blocks:

–Local anesthetic deposited near a larger terminal branch of a nerve

• Periapical injections-

Maxillary anesthesia:

• Nerve blocks:

–Local anesthetic deposited near maierve trunk and is usually distant from operative site

• Posterior superior alveolar – Infraorbital

• Middle superior alveolar – Greater palatine

• Anterior superior alveolar – Nasopalatine

Maxillary anesthesia:

• Posterior superior alveolar nerve block:

–Used to anesthetize the pulpal tissue, corresponding alveolar bone, and buccal gingival tissue to the maxillary 1st , 2nd and 3rd molars.

Maxillary anesthesia:

• Posterior superior alveolar nerve block:

–Technique

• Area of insertion- height of mucobuccal fold between 1st and 2nd molar

• Angle at 45° superiorly and medially

• No resistance should be felt (if bony contact angle is to medial, reposition laterally) • Insert about 15- -20mm

• Aspirate then inject if negative

Maxillary anesthesia:

• Middle superior alveolar nerve block:

–Used to anesthetize the maxillary premolars, corresponding alveolus, and buccal gingival tissue

–Present in about 28% of the population

–Used if the infraorbital block fails to anesthetize premolars

Maxillary anesthesia:

• Middle superior alveolar nerve block:

– Technique:

• Area of insertion is height of mucobuccal fold in area of 1st /2nd premolars

• Insert around 10- 15mm

• Inject around 0.9- -1.2cc

Maxillary anesthesia:

• Anterior superior alveolar nerve block:

–Used to anesthetize the maxillary canine, lateral incisor, central incisor, alveolus, and buccal gingiva

Maxillary anesthesia:

• Anterior superior alveolar nerve block:

–Technique:

• Area of insertion is height of mucobuccal fold in area of lateral incisor and canine area of lateral incisor and canine

• Insert around 10 15mm

• Inject around 0.9 -1.2cc

Maxillary anesthesia:

• Infraorbital nerve block:

–Used to anesthetize the maxillary 1st and 2 nd premolars, canine, lateral incisor, central incisor, corresponding alveolar bone, and buccal gingiva

–Combines MSA and ASA blocks

–Will also cause anesthesia to the lower eyelid, lateral aspect of nasal skin tissue, and skin of infraorbital region

Maxillary anesthesia:

• Infraorbital nerve block:

–Technique:

• Palpate infraorbital foramen extraorally and place thumb or index finger on region

• Retract the upper lip and buccal mucosa

• Area of insertion is the mucobuccal fold of the 1st premolar/canine area

• Contact bone in infraorbital region

• Inject 0.9- 1.2cc of local anesthetic

Maxillary anesthesia:

• Greater palatine nerve block:

–Can be used to anesthetize the palatal soft tissue of the teeth posterior to the maxillary canine and corresponding alveolus/hard palate

Maxillary anesthesia:

• Greater palatine nerve block:

Technique:

• Area of insertion is ~1cm medial from 1st /2nd maxillary molar on the hard palate • • Palpate with needle to find greater palatine foramen

• Depth is usually less than 10mm

• Utilize pressure with elevator/mirror handle to desensitize region at time of injection

• Inject 0.3- 0.5cc of local anesthetic

Maxillary anesthesia:

• Nasopalatine nerve block:

–Can be used to anesthetize the soft and hard tissue of the maxillary anterior palate from canine to canine

Maxillary anesthesia:

• Nasopalatine nerve block:

–Technique:

• Area of insertion is incisive papilla into incisive foramen

• Depth of penetration is less than 10mm

• Inject 0.3- 0.5cc of local anesthetic

• Can use pressure over area at time of injection to decrease pain

Maxillary anesthesia:

• Maxillary nerve block (V2 block):

–Can be used to anesthetize maxillary teeth, alveolus, hard and soft tissue on the palate, gingiva, and skin of the lower eyelid, lateral aspect of nose, cheek, and upper lip skin and mucosa on side blocked

Maxillary anesthesia:

• Maxillary nerve block (V2 block):

–Two techniques exist for blockade of V2

• High tuberosity approach

• Greater palatine canal approach

Maxillary anesthesia:

• Maxillary nerve block (V2 block):

–High tuberosity approach technique:

• Area of injection is height of mucobuccal fold of maxillary 2 nd molar

• Advance at 45° superior and medial same as in the PSA block

• Insert needle ~30mm

• Inject ~1.8cc of local anesthetic

Maxillary anesthesia:

• Maxillary nerve block (V2 block):

–Greater palatine canal technique:

• Area of insertion is greater palatine canal

• Target area is the maxillary nerve in the pterygopalatine fossa

• Perform a greater palatine block and wait 3- -5 min

• Then insert needle in previous area and walk into greater palatine foramen

• Insert to depth of ~30mm

• Inject 1.8cc of local anesthetic

Mandibular anesthesia:

• Infiltration techniques do not work in the adult mandible due to the dense cortical bone

• Nerve blocks are utilized to anesthetize the inferior alveolar, lingual, and buccal nerves

• • Provides anesthesia to the pulpal, alveolar lingual and buccal gingival tissue, and skin of lower lip and medial aspect of chin on side injected

Mandibular anesthesia:

• Inferior alveolar nerve block (IAN):

–Technique involves blocking the inferior alveolar nerve prior to entry into the mandibular lingula on the medial aspect of the mandibular ramus

–Multiple techniques can be used for the IAN nerve block

• IAN

• Akinosi

• Gow– Gates

Mandibular anesthesia

• Inferior alveolar nerve block (IAN):

–Technique:

• Area of insertion is the mucous membrane on the medial border of the mandibular ramus at the intersection of a horizontal line (height of injection) and vertical line (anteroposterior plane)

• Height of injection- – 6 -10 mm above the occlusal table of the mandibular teeth

• Anteroposterior plane- just lateral to the pterygomandibular raphe

Mandibular anesthesia:

• Inferior alveolar nerve block (IAN):

–Mouth must be open for this technique, best to utilize mouth prop

–Depth of injection: 25mm

–Approach area of injection from contralateral premolar region

–Use the non- dominant hand to retract the buccal soft tissue (thumb in coronoid notch of mandible; index finger on posterior border of extraoral mandible)

Mandibular anesthesia:

• Inferior alveolar nerve block (IAN):

–Inject ~0.5 1.0cc of local anesthetic

–Continue to inject ~0.5cc on removal from injection site to anesthetize the lingual branch

–Inject remaining anesthetic into coronoid notch region of the mandible in the mucous membrane distal and buccal to most distal molar to perform a long buccal nerve block

Mandibular anesthesia:

• Akinosi closed- mouth mandibular block:

–Useful technique for infected patients with trismus, fractured mandibles, mentally handicapped individuals, children

–Provides same areas of anesthesia as the IAN nerve block

Mandibular anesthesia:

• Akinosi closed- mouth mandibular block:

–Area of insertion: soft tissue overlying the medial border of the mandibular ramus directly adjacent to maxillary tuberosity

–Inject to depth of 25mm

–Inject ~1.0- 1.5cc of local anesthetic as in the IAN

–Inject remaining anesthetic in area of long buccal nerve

Mandibular anesthesia:

• Mental nerve block:

–Mental and incisive nerves are the terminal branches for the inferior alveolar nerve branches for the inferior alveolar nerve

–Provides sensory input for the lower lip skin, mucous membrane, pulpal/alveolar tissue for the premolars, canine, and incisors on side blocked

Mandibular anesthesia:

• Mental nerve block:

–Technique:

• Area of injection mucobuccal fold at or anterior to the mental foramen. This lies between the mandibular premolars

• Depth of injection 5- 6mm

• Inject 0.5- 1.0cc of local anesthesia

• Message local anesthesia into tissue to manipulate into mental foramen to anesthetize the incisive branch

Local anesthetics:

• Types:

– Esters- plasma pseudocholinesterase

–Amides- liver enzymes

• Duration of action:

–Short

–Medium

–Long

Local anesthetics:

• Dosing considerations:

–Patient with cardiac history:

• Should limit dose of epinephrine to 0.04mg

• Most local anesthesia uses 1:100,000 epinephrine concentration (0.01mg/ml)

–Pediatric dosing:

• Clark’s rule:

–Maximum dose=(weight child in lbs/150) X max adult dose (mg)

• Simple method= 1.8cc of 2% lidocaine/20lbs

Local anesthesia complications:

• Needle breakage

• Pain on injection

• Burning on injection

• Persistent anesthesia/parathesia

• Trismus

• Hematoma

• Infection

Local anesthesia complications:

• Edema

• Tissue sloughing

• Facial nerve paralysis

• Post- anesthetic intraoral lesion

–Herpes simplex

–Recurrent aphthous stomatitis

Local anesthesia complications:

• Toxicity

–Clinical manifestations

• Fear/anxiety

• Restlessness

• Throbbing headaches

• Tremors

• Weakness

• Dizziness

• Pallor

• Respiratory difficulty/palpitations

• Tachycardia (PVCs V- tach, , V- fib)

Local anesthesia complications:

• Allergic reaction:

–More common with ester based local anesthetics

–Most allergies are to preservatives in pre- made local anesthetic carpules

• Methylparaben

• Sodium bisulfite

• metabisulfite

Prolonged Anesthesia or Paresthesia

Complete anesthesia or an altered sensation in the lip or tongue may persist beyond the expected duration of action of a local anesthetic. Commonly referred to as a paresthesia, these neuropathies may manifest as a total loss of sensation (anesthesia), a burning or tingling, pain to non-noxious stimuli (dysesthesia), or increased pain to noxious stimuli (hyperesthesia).2,3 Prolonged anesthesia or paresthesia in the tongue or lip is known to occur following surgical procedures such as extractions,4,5 and it is assumed that the cause is direct trauma to either the lingual or inferior alveolar nerve. However, persistent anesthesia or paresthesia can also occur following nonsurgical dentistry. Most these are transient and resolve within eight weeks, but they may become irreversible. Whereas the former are an annoyance for the patient, the latter are much more distressing.

There are several putative causes of postinjection paresthesia. Hemorrhage into the nerve sheath may lead to an intraneural hematoma, which then causes pressure oerve fibers, impairing normal conduction. The hematoma and associated edema usually resorb within several weeks, and symptoms subsequently resolve. If scar formation results, there may be permanent loss of sensation. Direct trauma by the needle may also lead to similar damage. In addition, administration of local anesthetic from a cartridge contaminated by alcohol or sterilizing solution may induce paresthesia.6 Finally, neurotoxicity may be a factor, since a review of the literature suggests that local anesthetics have this potential.7-12

How often do paresthesias occur ionsurgical dentistry? A recent study led to an estimated incidence of 1 irreversible paresthesia out of every 785,000 injections.13 It has been stated in a legal case in Canada that this low frequency would not warrant advising every dental patient of this risk prior to each injection.14 This same study did note that specific drugs were more likely to be associated with paresthesia. Two drugs, articaine (which is available in Canada and parts of Europe under the trade name Ultracaine, among others) and prilocaine (Citanest), were more likely to be associated with paresthesia compared with the other anesthetics, and this was statistically significant when compared to the distribution of use.13 These same two drugs were again found to be significantly more likely to be associated with paresthesia in 1994.15

The reasons for this relationship to the type of anesthetic are speculative only. Differences in metabolism of these drugs would not be relevant since it occurs in organs away from the site of the neuropathy. Their only common feature is that they are the only injectable local anesthetics in dentistry that have a concentration of 4 percent, whereas the others are lower. It may be conjectured that toxicity may manifest simply because of the higher concentration of these drugs, as opposed to any unique characteristic. Needle trauma to the nerve combined with deposition of a large quantity of drug may be more likely to induce residual nerve damage. Supporting a role of drug concentration are reports of neurologic deficits in animal studies using 4 percent lidocaine16 and in human studies of spinal anesthetics with 5 percent lidocaine.10,11,17 This should be contrasted with the rare reports of neuropathy with 2 percent lidocaine (Xylocaine, among others), which is used in dentistry.

Prevention

There is no guaranteed method to prevent paresthesia or prolonged anesthesia. The inferior alveolar nerve block requires the practitioner to advance the needle near the inferior alveolar and lingual nerves. Practitioners attempt to place the needle near these nerves without intentionally striking them, yet this can occur and may be perceived as an “electric shock” sensation by the patient. Interestingly, this sensation does not imply that paresthesia will result.13 Directly contacting these nerves is not an indication of improper technique, it is simply a risk of carrying out intraoral injections.

Prevention of prolonged anesthesia or paresthesia:

If the patient feels “electric shock,” move needle away from this site prior to injecting.

Do not store cartridges of local anesthetic in disinfecting solutions.

Most paresthesias are transient and resolve within eight weeks. This is fortunate as there is no definitive means of improving the patient’s symptoms. The dentist must show concern and reassure the patient that these events can occur and usually resolve over time. The dentist should note the signs and symptoms and maintain contact with the patient. A change in the character of the symptoms can be an encouraging sign that there may be resolution of the neuropathy. It may indicate that there is healing of the nerve, and with time the patient may regaiormal sensation. The patient who has had no change in symptoms over a prolonged period, such as several months, is less likely to have a satisfactory outcome. Restoring sensation by microsurgery may be considered by those with training in this area. It has been stated that microsurgery is most likely to be successful if the patient is evaluated within the first month2 or the first three months.5 There is no guaranteed method of treating prolonged anesthesia or paresthesia.

Management of prolonged anesthesia or paresthesia:

Reassure the patient that the condition is usually temporary although, rarely, it can remain indefinitely.

Note signs and symptoms and follow up within one month.

If symptoms persist for more than two months, refer to an oral and maxillofacial surgeon with experience in this field.

Trismus

Limited jaw opening, or trismus, is a relatively common complication following local anesthetic administration. It can be caused by spasm of the muscles of mastication, which in turn may be a result of needle insertion into or through one of them. The most common muscle to be the source of trismus is the medial pterygoid, which can be penetrated during an inferior alveolar nerve block using any of the three main techniques: the conventional approach, the Vazirani-Akinosi (closed-mouth) technique, or the Gow-Gates. Rarely, the temporalis may be penetrated before it attaches onto the coronoid process if the needle is inserted too far laterally. Even more rarely, the lateral pterygoid muscle may be penetrated if a block is administered too far superiorly. Bleeding into the muscle following injection may also cause muscle spasm and trismus. Furthermore, injection of local anesthetic directly into muscle may cause a mild myotoxic response that can lead to necrosis.18 In the rare situation of an infection from the injection, trismus may also develop.

The main symptom of trismus is the limitation of movement of the mandible, which is often associated with pain. Symptoms will arise from one to six days following an injection. The duration of symptoms and their severity are both variable. Following management, as described below, improvement should be noted within two to three days. If there is no improvement within this time, the dentist should consider other possible causes, such as infection, and treat accordingly.

Prevention of trismus:

Follow basic principles of atraumatic injection technique.19

Management of trismus:

Apply hot, moist towels to the site for approximately 20 minutes every hour.

Use analgesics as required.

The patient should gradually open and close mouth as a means of physiotherapy.

Hematoma

A hematoma is a localized mass of extravasated blood that may become clinically noticeable following an injection. In this context, it can occur following the inadvertent nicking of a blood vessel during the penetration or withdrawal of the needle. When carrying out intraoral injections, practitioners often pierce blood vessels; but only when there is sufficient blood leaking out can a hematoma be seen. The vessels most commonly associated with hematomas are the pterygoid plexus of veins, the posterior superior alveolar vessels, the inferior alveolar vessels, and the mental vessels. The patient will notice development of swelling and the discoloration of a bruise lasting seven to 14 days. It is important to note that a hematoma will form independently of aspiration results. A negative aspiration does not guarantee an absence of a hematoma, as the needle may nick a blood vessel either on the way in or upon withdrawal. Aspiration results merely report the contents at the needle tip at the time of aspirating. Similarly, a positive aspiration does not imply that a hematoma will result, since the needle may simply have entered a vein at the time of aspiration, and the amount of blood leaking out from this vessel penetration may be clinically unnoticeable.

Prevention of hematoma:

Follow basic principles of atraumatic injection technique.19

Minimize the number of needle penetrations into tissue.

Use a short needle for the posterior superior alveolar nerve block.

Management of hematoma:

If visible immediately following the injection, apply direct pressure, if possible.

Once bleeding has stopped, discharge the patient with instructions to:

Apply ice intermittently to the site for the first six hours.

Do not apply heat for at least six hours.

Use analgesics as required.

Expect discoloration.

If difficulty in opening occurs, treat as with trismus, described above.

Pain on Injection

Occasionally, injection of local anesthetic can be accompanied by pain or a burning sensation. Passing the needle through a sensitive structure such as muscle or tendon may cause pain. It may occur during injection if the solution is administered too quickly and therefore distends the tissue rapidly. Local anesthetic solutions that are too cold or too warm may also cause discomfort. Solutions that are more acidic, namely those with vasoconstrictor, may cause a short-lasting burning sensation. Cartridges stored in a disinfecting solution such as alcohol may have residual amounts of solution on the end of the cartridge that can then be administered inadvertently during injection.

Prevention of pain:

Inject slowly: Take at least one minute to administer one cartridge.

Store cartridges at room temperature.

Do not store cartridges of local anesthetic in disinfecting solutions.

Management of pain:

Pain or burning on injection is usually self-limiting because it is treated by the onset of anesthesia.

Needle Breakage

This event is very rare. Sudden, unexpected movement of the patient is the primary cause.20,21 It is believed that smaller-diameter needles, i.e., 30 gauge, are more likely to break than larger-diameter, i.e., 25 gauge. Needle breakage usually occurs at the hub, which is the reason for never inserting a needle completely into tissue. Although bending a needle may be considered for injection techniques such as the Vazirani-Akinosi or the maxillary nerve block,22-24 some advise against this practice.25 If it is done, it is important to do so only once because repeated bending will weaken the connection at the hub and predispose the needle to breakage.

Prevention of needle breakage:

Do not insert a needle into tissues up to its hub; always leave a portion exposed.

Use long needles if a depth of more than 18 mm is required.

Use larger-diameter needles (25 gauge is ideal) for the deeper blocks, such as the three mandibular block techniques (conventional, Gow-Gates, and Vazirani-Akinosi) and the maxillary nerve block.

Do not apply excessive force on the needle once it is inserted in tissue.

If redirecting a needle is required, withdraw it almost completely before doing so.

Do not bend a needle more than once.

Management of needle breakage:

Remain calm.

Ask the patient to remain still; keep their mouth open by not removing your hand.

If a portion of the needle is visible, remove it with a hemostat or similar instrument.

If the needle is not visible:

Inform the patient.

Record the events in the chart.

Refer the patient to an oral and maxillofacial surgeon.

Surgical removal should only be attempted by someone experienced with surgery of the involved region and after radiographs have been taken to help localize the needle.26

Soft Tissue Injury

With the loss of sensation that accompanies a successful block, a patient can easily bite into his or her lip or tongue. Swelling and pain will result following the offset of anesthesia. This event is most common in children or patients who are mentally challenged or demented, such as those with Alzheimer’s disease. The child’s parent or guardian, or the caregiver with the mentally challenged patient or those with dementia, should be advised to carefully observe the patient for the expected duration of anesthesia. Nevertheless, soft tissue injury may also be a concern for mentally normal patients who are at risk of an exaggerated response to trauma.

Prevention of soft tissue injury:

For pediatric, mentally challenged, or demented patients, use a local anesthetic of appropriate duration.

Warn the parent, guardian, or caregiver to watch the patient carefully for the duration of soft-tissue anesthesia to prevent biting of tissue.

In children, consider placing a cotton roll between the mucobuccal fold for the duration of anesthesia.

Explain the risks of soft tissue injury to patients with bleeding abnormalities.

Management of soft tissue injury:

Use analgesics as required.

Use rinses or applications with lukewarm dilute solutions of salt or baking soda.

Consider applying petroleum jelly over lip lesion.

Facial Nerve Paralysis

Anesthesia of the facial nerve may occur if the needle has penetrated the parotid gland capsule and local anesthetic is then administered within. This nerve, the seventh cranial nerve, is contained within the parotid gland and provides motor function through its five branches — the temporalis, zygomatic, buccal, mandibular and cervical. Needle placement into the parotid may occur if there is overinsertion during an inferior alveolar nerve block or the Vazirani-Akinosi block. The result of anesthesia of these branches of this nerve includes a transient unilateral paralysis of the muscles of the chin, lower lip, upper lip, cheek, and eye. There will be a loss of tone in the muscles of facial expression. In the past, the term Bell’s palsy was commonly used to refer to all paralyses of the facial nerve, but it is now restricted to those induced virally.27

Facial nerve paralysis secondary to local anesthetic injection is temporary and will last the expected duration of anesthesia of soft tissue for the particular anesthetic administered. There are risks if there is a loss of the protective reflex to close the eyelid. An example of the appearance of a patient with a transient facial nerve paralysis is shown in Figure 3.

Unwanted anesthesia of other nerves may also occur. Ocular complications following temporary paralysis of cranial nerves III, IV, or VI,28,29 as well as the optic nerve,30 have been described. The proposed mechanism for these events is intravenous transport of local anesthetic to the cavernous sinus.31 Careful aspiration to avoid intravenous injection should prevent this complication.

Prevention of facial nerve paralysis:

Follow basic principles of atraumatic injection technique.19

Avoid overinsertion of the needle.

For the conventional inferior alveolar nerve block, do not inject unless bone has been contacted at the appropriate depth.

Management of facial nerve paralysis:

Reassure the patient of the transient nature of the event.

Advise the patient to use an eye patch until motor function returns.

If contact lenses are worn, they should be removed.

Record details in the patient’s chart.

Infection

With the introduction many years ago of sterile disposable needles, infection is now an extremely rare complication of local anesthetic administration. It may occur if the needle has been contaminated prior to insertion. The normal flora of the oral cavity is not a concern since they do not lead to infection in patients who are not significantly immunocompromised. In fact, bacteria enter the tissues with every needle insertion, yet the body’s normal defense prevents a clinical infection. In patients who are severely immunocompromised, a topical antiseptic or an antiseptic rinse such as chlorhexidine could be considered prior to needle insertion.

If an infection does occur, it will likely manifest initially as pain and trismus one day postinjection. If these symptoms persist for three days and continue to worsen, the possibility of infection should be considered. At this stage, this patient should be examined for other signs of infection, such as swelling, lymphadenopathy, and fever.

When there is an active site of infection, such as an abscess, needles should not be inserted. This is not only because the low pH will prevent the onset of local anesthetic action, but also because there is the potential for spreading the infection.

Prevention of infection:

Use sterile disposable needles.

Do not contaminate the needle by contacting nonsterile surfaces outside the mouth.

In severely immunocompromised patients, consider a topical antiseptic prior to injection.

Management of infection:

Prescribe antibiotics, such as penicillin, in an appropriate dose and duration.

Record details in the patient’s chart and follow up to determine progress.

Mucosal Lesions

Occasionally, the intraoral mucosa may show signs of sloughing or ulceration. The epithelial layer may desquamate from prolonged application of topical anesthetic. It is possible, but not common, that necrosis of tissues may result from high concentrations of vasoconstrictor, such as 1:50,000. Sites of ulceration consistent with a diagnosis of aphthous stomatitis may also result following local anesthetic administration. For each of these, the lesions will be present for one to two weeks and resolve irrespective of treatment. Drug therapy is seldom warranted. Simple measures such as saline or sodium bicarbonate rinses may assist healing by keeping the sites relatively clean.

Prevention of mucosal lesions:

Do not leave topical anesthetic on mucosa for prolonged periods.

Management of mucosal lesions:

Reassure the patient; advise him or her of the expected duration of one to two weeks.

Use rinses with lukewarm dilute solutions of salt or baking soda, until symptoms resolve.

Pharmacology of inhalation and

intravenous sedation

INTRODUCTION

A sound understanding of the principles of the phamacology

of the individual sedation agents is essential to the safe practice

of sedation. It is important from the outset to specify exactly

what is meant by a sedation agent, as there can be considerable

overlap between drugs which produce both sedation and

general anaesthesia. A drug used for sedation should:

1. Depress the central nervous system (CNS) to an extent that

allows operative treatment to be carried out with minimal

physiological and psychological stress

2. Modify the patient’s state of mind such that communication

is maintained and the patient will respond to spoken

command

3. Carry a margin of safety wide enough to render the

unintended loss of consciousness and loss of protective

reflexes unlikely.

Current sedation practice should only use agents and

techniques which satisfy the above criteria. Additionally, the

agents themselves should have a:

1. Simple method of administration

2. Rapid onset

3. Predictable action and duration

4. Rapid recovery

5. Rapid metabolism and excretion

6. Low incidence of side effects.

Sedation agents are usually administered via the inhalation,

intravenous or oral routes. The route of administration affects

the timing of drug action, although ultimately all drugs arrive

at their target cells in the brain via the bloodstream.

Inhalation agents have the advantage of being readily

absorbed by the lungs to provide a rapid onset of sedation,

followed by rapid elimination and recovery. Intravenous agents

4 Pharmacology of inhalation and

intravenous sedation

are predictably absorbed but once administered cannot be

removed from the bloodstream. The therapeutic action of

intravenous agents is terminated by re-distribution,

metabolism and excretion. Oral sedatives have a less certain

absorption due to variability of gastric emptying and they

therefore produce unpredictable levels of sedation.

This chapter will primarily address the pharmacology of

sedation agents currently used in inhalation and intravenous

techniques. The pharmacology of the oral sedatives not

included in this chapter, will be covered in Chapter 5.

INHALATION SEDATION AGENTS

Inhalation agents produce sedation by their action on various

areas of the brain. They reach the brain by entering the lungs,

crossing the alveolar membrane into the pulmonary veins,

returning with the blood to the left side of the heart and then

passing into the systemic arterial circulation. Thus the two

main components of inhalation sedation are, the entry of the

inspired gas into the lungs and distribution of the agent by the

circulation to the tissues.

Basic pharmacology of inhalation sedatives

Gas solubility and partial pressure

During the induction of inhalation sedation, each breath of

sedation agent raises the partial pressure of the gas in the

alveoli. As the alveolar partial pressure rises, the gas is forced

across the alveolar membrane into the bloodstream, where it

is carried to the site of action in the brain. The gas passes down

a pressure gradient from areas of high partial pressure to areas

of low partial pressure (Figure 4.1). The level of sedation is

proportional to the partial pressure of the agent at the site of

action. After termination of gas administration the reverse

process occurs. The partial pressure in the alveoli falls and the

gas passes in the opposite direction out of the brain, into the

circulation and then into the lungs.

The rate at which a gas passes down its pressure gradient is

determined by its solubility. The solubility of a sedation agent

(i.e. the blood-gas partition coefficient) determines how quickly

the partial pressure in the blood and, ultimately the brain, will

rise or fall. The higher the partition coefficient, the greater the

alveolar concentration of the agent needs to be to produce a

rise in partial pressure in the blood and ultimately the tissues.

For the purposes of sedation, a gas with a low partition

coefficient is preferred. Small concentrations of gas will

Figure 4.1

Movement of nitrous

oxide gas down the

partial pressure gradient

during induction and

recovery from

inhalational sedation.

produce a rapid rise in partial pressure and a fast onset of

sedation. Similarly, after cessation of gas administration there

will be a rapid fall in partial pressure and a fast recovery.

It is the inspired concentration of sedation agent which

will determine the final level of sedation. The speed of

induction of sedation is influenced by the rate of increase in

gas concentration, as well as the minute volume and cardiac

output of the patient. Any increase in minute volume, such as

can be caused by asking the patient to take deep breaths, will

increase the speed of onset of sedation.

Conversely, an increase in cardiac output will reduce the

speed of induction of sedation. With a high cardiac output

there is an increased volume of blood passing through the

lungs. The sedation agent present in the lungs will be taken up

into this larger volume of blood and the actual concentration

of gas transported per unit volume of blood will be lower.

Thus, less sedation agent will reach the brain and there will

be a slower onset of sedation. The speed of recovery after

termination of gas administration is similarly affected by the

same factors.

Potency of inhalation sedation agents

All sedation agents will produce general anaesthesia if used

in high enough doses. The key to modern sedation practice is

to ensure that the agents used have a wide enough margin of

safety to render the unintended loss of consciousness unlikely.

This means that there should be a considerable difference in

the dose required to produce a state of sedation and the dose

needed to induce general anaesthesia. For inhalation anaesthetic agents the potency is expressed

in terms of a minimum alveolar concentration (MAC). The

MAC of an agent is the inspired concentration which will, at

equilibrium, abolish the response to a standard surgical

stimulus in 50% of patients.

Although the inspired concentration is measured as a

percentage, the MAC is usually expressed as a number.

Equilibrium is achieved when the tissue concentration of the

gas equals the inspired concentration. MAC is a useful index

of potency and is used to compare different anaesthetic gases.

Gases used for sedation should preferably have a moderate

or high MAC and a low solubility. This will ensure a broad

margin of safety between the incremental doses used to

produce sedation and the final concentration required to

induce anaesthesia. It would be very easy, using an agent

with a small MAC for sedation, to accidentally overdose and

anaesthetise a patient.

Types of inhalation sedation agents

Nitrous oxide

Nitrous oxide is the only inhalation agent currently in routine

use for conscious sedation in dental practice. It was discovered

by Joseph Priestly in 1772 and first used as an anaesthetic agent

for dental exodontia by Horace Wells in 1844. Nitrous oxide

has been used as the basic constituent of gaseous anaesthesia

for the subsequent 160 years, demonstrating its acceptability

and usefulness. In the 1930s, nitrous oxide was used for

sedation purposes in the Scandinavian countries, particularly

Denmark. However, it was not until the 1960s, when Harold

Langa pioneered the modern practice of relative analgesia that

nitrous oxide came into widespread use as an inhalation

sedation agent in dentistry.

Presentation: Nitrous oxide is a colourless, faintly sweetsmelling

gas with a specific gravity of 1.53. It is stored in light

blue cylinders in liquid form at a pressure of 750 pounds per

square inch (43.5 bar).

The gas is sold by weight and each cylinder is stamped with

its empty weight. As the contents of the cylinder are liquid, the

pressure inside, as measured by the pressure gauge on the

inhalational sedation machine, will remain constant until nearly

all the liquid has evaporated. The value shown on the gauge

does not decrease in a linear fashion and tends to fall rapidly

immediately before the cylinder becomes empty (Figure 4.2).

Thus, the only reliable means of assessing the amount of

nitrous oxide in a cylinder is to weigh the cylinder and compare

the value with the weight of the empty cylinder. It can also be

Figure 4.2

The pressure in the

nitrous oxide cylinder

remains constant and

tends to fall rapidly

immediately before the

cylinder becomes empty.

tapped with a metal instrument by those with musical ears;

the pitch of the note falls as the gas is used. In addition, after

prolonged use, the evaporation of the liquid nitrous oxide

causes ice crystallisation on the cylinder at the level of the

liquid within, thereby providing a third indication as to the

nitrous oxide volume remaining in the cylinder.

Blood/gas solubility: Nitrous oxide has a low blood-gas

partition coefficient of 0.47, so it is relatively insoluble and

produces rapid induction of sedation. A further consequence of

the poor solubility is that, when administration is discontinued,

nitrous oxide dissolved in the blood is rapidly eliminated via

the lungs. During the first few minutes of this elimination, large

volumes of nitrous oxide pour out of the blood and into the

lungs. This can actually displace oxygen from the alveoli

causing a condition known as diffusion hypoxia. This occurs

because the volume of nitrous oxide in the alveoli is so high that

the patient effectively ‘breathes’ 100% nitrous oxide. For this

reason the patient should receive 100% oxygen for a period

of at least 2–3 minutes after the termination of nitrous oxide

sedation. In reality, the risk of diffusion hypoxia is minimal due

to the high level of oxygen delivered by dedicated inhalation

sedation machines.

Potency: Nitrous oxide has a theoretical minimum alveolar

concentration (MAC) of about 110. The high MAC means

that nitrous oxide is a weak anaesthetic which is readily

titrated to produce sedation. Because the MAC is over 80, it is

theoretically impossible to produce anaesthesia using nitrous

oxide alone, at normal atmospheric pressure, in a patient

who is adequately oxygenated. However, caution should be

exercised when using inhaled concentrations of nitrous oxide

over 50%, because even at this relatively low percentage, some

patients may enter a stage of light anaesthesia.

Sedation: Nitrous oxide is a good, but mild sedation agent

producing both a depressant and euphoriant effect on the CNS.

It is also a fairly potent analgesic. A 50% inhaled concentration

of nitrous oxide has been equated to that of parenteral

morphine injection at a standard dose (10mg in a 70kg adult).

It can be used to good effect to facilitate simple dentistry in

patients who are averse to local analgesia and it decreases the

pain of injections in those who require supplemental local

anaesthesia. Nitrous oxide has few side effects in therapeutic

use. It causes minor cardio-respiratory depression, and

produces no useful amnesia.

Occupational hazards of nitrous oxide: The main problems

associated with the use of nitrous oxide relate not to the patient

but to the staff providing sedation, and the potential hazards

of chronic exposure to nitrous oxide gas have recently been

recognised. It has been shown that regular exposure of

healthcare personnel to nitrous oxide can cause specific

illnesses, the most common effects being haematological

disorders and reproductive problems (Figure 4.3).

Figure 4.3

Hazards of chronic

exposure to nitrous

oxide.

It is well known that nitrous oxide causes the oxidation

of vitamin B12 and affects the functioning of the enzyme

methionine synthetase. This in turn impairs haematopoesis

and can give rise to pernicious anaemia in staff exposed to

nitrous oxide for prolonged periods (Figure 4.4).

Dental clinicians who have abused nitrous oxide have been

shown to have the debilitating neurological signs of pernicious

anaemia. It has been shown that where unscavenged nitrous

oxide has been used, there may be an increase in the rate of

miscarriages in female dental surgeons, dental nurses and,

perhaps surprisingly, in the wives of male dental surgeons who

have been exposed to nitrous oxide gas. Dental nurses assisting

with nitrous oxide sedation, where scavenging is not provided,

are also twice as likely to suffer a miscarriage as other dental

Figure 4.4

Biochemical effect of

chronic nitrous oxide

exposure.

nurses. Chronic exposure to nitrous oxide has also been shown

to be associated with decreased female and male fertility. Other

chronic effects of nitrous oxide exposure are much rarer but

are said to include hepatic and renal disease, malignancy and

cytotoxicity.

It should be noted that it is the cumulative effect of the gas

which is the major concern and that the effects of the nitrous

oxide very much depend on:

1. The pattern of exposure

2. Tissue sensitivity

3. Vitamin B12 intake and body stores

4. Extent to which methionine synthetase is deactivated.

The subject of nitrous oxide pollution has become a worldwide

health and safety issue, particularly as it is described as a

‘greenhouse gas’ and appears to contribute to the damage of

the ozone layer. Regulations have therefore been put in place

to define the maximum acceptable occupational exposure

of personnel to nitrous oxide. In the UK, exposure should not

average more than 100 ppm over an 8-hour period under the

current health and safety regulations. Since the initial studies

into the effects of chronic exposure in healthcare personnel

working with nitrous oxide, the risks have been reduced

considerably by the introduction of efficient scavenging and

ventilation systems. If exhaled nitrous oxide is actively removed

there will be less pollution of the atmosphere where healthcare

personnel are working. Better training and understanding ofthe technique has also led to more efficient and effective

provision of inhalation sedation.

Sevoflurane

Sevoflurane is receiving much attention in the field of

sedation research as a possible agent for use in dentistry. It is

a sweet-smelling, non-flammable, volatile anaesthetic agent

used for induction and maintenance of general anaesthesia.

Sevoflurane is a potent agent with a MAC value of under 2,

leaving it with a narrow margin of safety. Its use in sedation

necessitates the use of a specialised vapouriser to ensure

levels are kept to a subanaesthetic level of 0.3%. Other volatile

anaesthetic agents such as halothane and isoflurane have also

been tested for use in inhalational sedation. Unfortunately

they are even more potent drugs than sevoflurane, with low

MAC values (the MAC of halothane is 0.76). This again reduces

the margin of safety and makes the induction of general

anaesthesia more likely. These drugs are not currently suitable

for providing sedation in dental practice and do not comply

with the basic definitions of safe sedation, however research

into the use of sevoflurane is promising.

Oxygen

Oxygen is not a sedation agent, however, inhalation sedation

agents are always delivered in an oxygen-rich mixture

containing a minimum of 30% oxygen by volume. Oxygen is

stored as a gas in black cylinders with white shoulders, at an

initial pressure of 2000 pounds per square inch (137 bar).

Because it is a gas under pressure, the gauge on the

inhalational sedation machine will give an accurate

representation of the amount of oxygen contained in the

cylinder. The oxygen supply used for inhalational sedation

should be separate from, and additional to, the supply kept for

use in the management of emergencies. Oxygen will sustain

and enhance combustion and therefore no naked flames

should be allowed in an area where oxygen is being used.

INTRAVENOUS SEDATION AGENTS

Intravenous sedation agents are injected directly into the

bloodstream where they are carried in the plasma to the tissues.

The plasma level of the sedative attained during injection

causes the agent to diffuse down its concentration gradient and

across the lipid membranes to the site of action in the brain.

The factors which influence the plasma level of the drug are

Pharmacology of inhalation and intravenous sedation 65

therefore instrumental in determining the onset of action and

recovery from the effect of the sedation agent.

BASIC PHARMACOLOGY OF INTRAVENOUS

SEDATIVES

Induction of sedation

Upon intravenous injection the plasma level of a sedation drug

will rise rapidly. The agent will pass through the venous system

to the right side of the heart and then via the pulmonary

circulation to the left side of the heart. Once in the arterial

system it will reach the brain but it will only start to have its

effect once diffusion across the lipid membranes has occurred.

The effect of sedation will normally commence in one armbrain

circulation time, approximately 35 seconds. The final

plasma concentration of the sedation agent will depend on the

total dose of drug, the rate of the injection, the cardiac output

and the circulating blood volume. The greater the dose of drug

injected and the faster the rate of injection then the higher the

plasma concentration. In contrast, the higher the cardiac

output and/or the blood volume, the lower the plasma

concentration.

Recovery from sedation

Recovery from sedation occurs by two processes. The first is the

redistribution of the sedation agent from the CNS into the body

fat. The initial peak plasma concentration forces the sedation

agent into tissues which are well-perfused such as the brain,

heart, liver and kidneys. With time, an increasing amount of the

sedation agent is taken into adipose tissue. Although solubility

in fat is lower than in well-perfused tissues, the high mass of

the body fat and the lipid solubility of sedation agents does

promote redistribution to the fat stores. Ultimately the plasma

concentration of drug falls and the blood-brain concentration

gradient is reversed. This forces the sedation agent out of the

brain and back into the bloodstream. The second process

involves the uptake and metabolism of the sedation agent in

the liver and elimination via the kidneys. This results in the

final reduction in plasma concentration leading to complete

recovery of the patient.

The relative importance of redistribution and elimination

depends on the individual sedation agent but in general,

redistribution is responsible for the initial recovery from

sedation (the alpha half-life; T1/2α), followed by elimination

of the remaining drug (the beta half-life; T1/2β). Virtually all

66 Clinical Sedation in Dentistry

intravenous agents have two half-lives. Only those with very

rapid metabolism do not demonstrate a bi-phasic curve. In

considering different drugs, however, it is the elimination

half-life which can be used to compare the pharmacokinetic

effects of different sedation agents.

Types of intravenous sedation agents

Benzodiazepines

It was not until the 1960s that agents were developed

specifically for conscious sedation. At this time a group of

tranquilising drugs known as the benzodiazepines were

discovered in Switzerland by researchers at Hoffman-La Roche.

Since then the benzodiazepines have become the mainstay

of modern sedation practice in the United Kingdom. The

first benzodiazepine to come on the market was diazepam

(Valium®). Since then, other drugs including midazolam and

temazepam have been developed which are used in the field of

dental sedation.

Pharmacokinetics: To understand the mechanism of action

of the benzodiazepines, it is necessary to appreciate the normal

passage of information through sensory neurones to the CNS.

A system made up of ‘GABA’ (gamma-amino-butyric-acid)

receptors is responsible for filtering or damping down sensory

input to the brain. GABA is an inhibitory chemical which is

released from sensory nerve endings as electrical nerve stimuli

pass from neurone to neurone over synapses. Once released,

GABA attaches itself to receptors on the cell membrane of the

post-synaptic neurone. The post-synaptic membrane becomes

more permeable to chloride ions which has the effect of

stabilising the neurone and increasing the threshold for firing

(Figure 4.5).

During this refractory period no further electrical stimuli

can be transmitted across the synapse. In this way the numbers

of sensory messages which travel the whole distance of the

neurones (from their origin to the areas of the brain where they

are perceived) are reduced or ‘filtered’. For every stimulus to

the senses (touch, taste, smell, hearing, sight), very many more

electrical stimuli are initiated than are necessary for the subject

to perceive the stimulus and react to it.

Benzodiazepines act throughout the CNS via the GABA

network. Specific benzodiazepine receptors are located close

to GABA receptors oeuronal membranes within the brain

and spinal cord. All benzodiazepines (which, like all sedatives,

are CNS depressants) have a similar shape, with a ring structure

(benzene ring) on the same position of the diazepine part of

each molecule. It is this common core shape which enables

Figure 4.5

Mechanism of action of

gamma-aminobutyric

acid (GABA).

them to attach to the benzodiazepine receptors. The effect of

having a benzodiazepine in place on a receptor, is to prolong

the time it takes for re-polarisation after a neurone has been

depolarised by an electrical impulse. This further reduces the

number of stimuli reaching the higher centres and produces

pharmacological sedation, anxiolysis, amnesia, muscle

relaxation and anticonvulsant effects. Benzodiazepines

act essentially by mimicking the normal physiological filter

system of the body and they may do so positively or negatively.

There is a range of benzodiazepines which vary from

those having the desired effects (agonists), to those having

the entirely opposite effect (inverse agonists). In the centre

of the spectrum is a group of drugs which have an affinity for

the benzodiazepine receptor but which are, to all intents and

purposes, pharmacologically inactive (antagonists).

Clinical effects: The clinical effects of the agonist

benzodiazepines include:

• Induction of a state of conscious sedation with acute

detachment for 20–30 minutes and a state of relaxation for

a further hour or so

• Production of anterograde amnesia (loss of memory in the

period immediately following the introduction of the drug)

• Muscle relaxation

• Anticonvulsant action

• Minimal cardiovascular and respiratory depression when

intravenous benzodiazepines are titrated slowly to a defined

end point of conscious sedation in healthy patients.

(Titration refers to the process of adding small increments

of a sedative whilst observing the clinical response until it is

deemed adequate)

Benzodiazepines do not produce any clinically useful

analgesia, although the sedation itself may alter the patient’s

response to pain.

Figure 4.5

Mechanism of action of

gamma-aminobutyric

acid (GABA).

68 Clinical Sedation in Dentistry

Side effects: Although intravenous benzodiazepines are

generally very safe sedation agents, they do have some

disadvantages, including:

• Respiratory depression

• Cardiovascular depression

• Over-sedation in older people and children

• Tolerance

• Sexual fantasy.

The most significant side effect is respiratory depression.

Some degree of respiratory depression occurs in all patients

sedated with the benzodiazepines but this usually only

becomes clinically significant in patients with impaired

respiratory function or in those who have taken other CNS

depressants or where the drug is administered too rapidly or

in a bolus dose .

Pre-existing respiratory disease: A patient with pre-existing

respiratory disease will already have a degree of respiratory

compromise and will be especially at risk from the respiratory

depressant effects of the benzodiazepines.

Synergistic effect: There is a synergistic relationship between

the benzodiazepines and certain other CNS depressants, such

as the opiates or alcohol. In a synergistic relationship, the effect

of two drugs is greater than the sum total of the individual

drugs and this is particularly noticeable with the opiates, when

required doses may be 25% or less than if a single drug had been

administered. The risk, therefore, of overdose in combined

drug techniques is significantly higher than when a single agent

is used.

Inappropriate drug administration: Excessively rapid

intravenous injection of the benzodiazepines can cause

significant respiratory depression which may result in

apnoea. This can be avoided by slow incremental injection of

the drug. If apnoea does occur, then assisted ventilation will

be required. It is also thought that the laryngeal reflexes may

be momentarily obtunded immediately following injection of

a benzodiazepine. Although this state is short-lived, the dental

clinician should always ensure that the patient’s airway is well

protected when performing dental treatment on sedated

patients.

Because of the risk of apnoea, it has been suggested by some

authorities that supplemental oxygen be used in all patients.

However, this is not universally practised and it is questionable

as to whether it is really indicated in fit, young healthy patients.

There is little doubt, however, that supplemental oxygen does

result in the maintenance of better oxygen saturation and it

should, therefore, be considered in cases where appropriate,

particularly in older or medically compromised patients.

Pharmacology of inhalation and intravenous sedation 69

The benzodiazepines also produce minor cardiovascular

side effects in healthy patients. They cause a reduction in

vascular resistance which results in a fall in blood pressure.

This is compensated by an increase in heart rate, and the

cardiac output and usually blood pressure are thus unaffected.

Older patients are particularly susceptible to the effects

of the benzodiazepines. It is relatively easy to overdose an

older patient and cause significant respiratory depression.

Intravenous benzodiazepines should be administered slowly

and in very small increments to older people. The total dose

required to produce sedation will be much smaller than in a

younger adult of the equivalent weight. The use of intravenous

benzodiazepines for children under the age of 16 years in a

primary care setting should be considered carefully. Children

may react more unpredictably to intravenous benzodiazepines

and can easily become over-sedated. Occasionally they may

show signs of disinhibition and become extremely distraught,

a reaction more common in the teenage years. Extreme care

needs to be undertaken with such patients, as the temptation

to keep adding further increments can easily result in an

unconscious patient. Treating children under intravenous

benzodiazepine sedation requires that the dental clinician is

appropriately trained in the use of this technique and is fully

competent in the provision of paediatric basic life support.

Patients who are already taking oral benzodiazepines

for anxiolysis or insomnia may be tolerant to the effect of

intravenous benzodiazepines. Those who have become

dependant on long-term benzodiazepine therapy may also

have their dependence reactivated by acute intravenous

administration.

There have also been reported incidents of sexual fantasy

occurring under intravenous benzodiazepine sedation but this

only seems to occur when higher than recommended doses of

the drug are administered.

Diazepam

Diazepam was the first benzodiazepine to be used in intravenous

sedation practice (see Figure 4.6). It is almost insoluble in water

and so it is either dissolved in an organic solvent, propylene

glycol (Valium®), or it is emulsified into a suspension in soya

bean oil (Diazemuls®). The organic solvent formulation caused

a high incidence of vein damage, ranging from pain to frank

thrombophlebitis and even skin ulceration, so this preparation

is no longer used. Diazemuls® is a non-irritant preparation

which overcomes the problem of venous damage.

Diazepam is metabolised in the liver and eliminated via the

kidneys. It has a long elimination half-life (T1/2β) of 43 hours(+/−13 hours) although its distribution half-life (T1/2α) is in the

region of 40 minutes. An active metabolite, n-desmethyldiazepam,

is produced, which can cause rebound sedation up to 72 hours

after the initial administration of diazepam.

Diazemuls® is presented in a 2ml ampoule in a

concentration of 5mg/ml for intravenous injection. It is a

reliable hypnosedative which should be given slowly, titrating

the dose against the response obtained. The standard dose lies

in the range 0.1-0.2mg/kg. Unfortunately the long recovery

period and possibility of rebound sedation mean that diazepam

in any form, is not the ideal drug for sedation for short dental

procedures and its use has largely been superseded by the

more modern and more rapidly metabolised midazolam.

Midazolam

Midazolam was introduced into clinical practice in 1983

although it had been synthesised several years previously (see

Figure 4.7). It is currently the agent of choice for intravenous

sedation in dentistry, however there are newer agents on the

horizon.

It is an imadazobenzodiazepine which is water soluble with

a pH of less than 4.0 and which is a non-irritant to veins. Once

injected into the bloodstream, at physiological pH, it becomes

lipid soluble and is readily able to penetrate the blood-brain

barrier. It has an elimination half-life of 1.9 hours (+/−0.9 hours)

so that complete recovery is quicker than that with diazepam.

Midazolam is more rapidly acting, at least 2.5 times as potent

and has more predictable amnesic properties, than diazepam.

It is rapidly metabolised in the liver but there is also some

extra-hepatic metabolism in the bowel. Midazolam producesan active metabolite called alpha-hydroxymidazolam. This

has a short half-life of 1.25 hours (+/−0.25 hours) which is less

than that of the parent compound and thus does not produce

true rebound sedation. It does, however, explain the clinically

observable phenomenon of a slower initial recovery from

midazolam sedation than would be expected, on the basis of

the pharmacokinetics of the drug, without reference to its

active metabolite.

Midazolam is available in two formulations: a concentration

of 5mg/ml in a 2ml ampoule, or a concentration of 2mg/ml in

a 5ml ampoule. Both presentations contain the same quantity

of midazolam but the 5ml ampoule presentation, being less

concentrated, is easier to titrate and is more acceptable for use

in dental practice. The dose of midazolam is titrated according

to the patient’s response but most patients require a dose

usually in the range of 0.07–0.1mg/kg.

Flumazenil (benzodiazepine antagonist)

The discovery of the benzodiazepine antagonist, flumazenil,

in 1978, was a major advance in the practice of intravenous

sedation. It was the first drug to effectively and completely

reverse the effects of almost all benzodiazepines. Flumazenil

is a true benzodiazepine but it has virtually no intrinsic

therapeutic activity (the administration of huge doses of

flumazenil may result in very slight epileptiform activity). It

shares the same basic chemical form as other benzodiazepines

but it lacks the ring structure attached to the diazepine part of

the molecule (Figure 4.8). It is this slight alteration in structure which prevents

flumazenil from having any genuine therapeutic activity.

Flumazenil has a greater affinity for the benzodiazepine

receptor than virtually all the known active drugs and it is

therefore an effective antagonist. It will reverse (at least on a

temporary basis) the sedative, cardiovascular and respiratory

depressant effects of both diazepam and midazolam – in fact

the vast majority of all commercially available enzodiazepines.

Flumazenil is presented in 5ml ampoules containing

500mcg/ml for intravenous injection. It is administered by

giving 200mcg and then waiting for 1 minute. A further 100mcg

is then given every minute until the patient appears fully

recovered. In an acute emergency there is no reason why higher

initial doses of up to 500mcg should not be given immediately

as a bolus. Flumazenil is currently only recommended for

use in emergency situations and not as a means of hastening

recovery. If flumazenil were used for routine reversal, there

is a theoretical risk that that the benzodiazepine sedation

may recur once the effect of the flumazenil had worn off.

This is because flumazenil has a shorter elimination half-life

(53 minutes, +/−13 minutes) than the active benzodiazepines.

For healthy patients this is a theoretical concept with little

basis in clinical practice and the greatest objections to using

flumazenil routinely are its cost and the rather sudden and

unpleasant ‘wakening’ which it produces. In patients who use

benzodiazpines on a long-term basis, it may be significantly

Functional gastrointestinal disturbances in the early age children

Diseases of the lips and tongue in children

Diaphragmatic hernia. Disease of mediastinum

IMMUNE PREPARATIONS

Lecture 1

Articulation and occlusion. Biomechanics of movement of the mandible (Vertical, sagittal, transversal movements of the mandible).

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ANATOMICAL AND PHYSIOLOGICAL FEATURES OF THE DEVELOPMENT AND STRUCTURE OF TISSUES AND ORGANS SCHLD IN CHILDREN

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Functional gastrointestinal disturbances in the early age children

Diseases of the lips and tongue in children

Diaphragmatic hernia. Disease of mediastinum

IMMUNE PREPARATIONS

Lecture 1

Articulation and occlusion. Biomechanics of movement of the mandible (Vertical, sagittal, transversal movements of the mandible).